RNA-Seq analysis of glioma tumors to reveal targetable gene fusions.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2019-2019 ◽  
Author(s):  
Deepa Suresh Subramaniam ◽  
Joanne Xiu ◽  
Shwetal Mehta ◽  
Zoran Gatalica ◽  
Jeffrey Swensen ◽  
...  
Keyword(s):  
Life Sciences ◽  
Gene Fusions ◽  
Astrocytic Tumors ◽  
Fusion Genes ◽  
Rna Seq ◽  
Wild Type ◽  
Oligodendroglial Tumors ◽  
Grade Ii ◽  
Glioma Tumors ◽  
Grade Iii

2019 Background: Fusions involving oncogenes have been reported in gliomas and may serve as novel therapeutic targets. We aim to use RNA-sequencing to interrogate a large cohort of gliomas for targetable genetic fusions. Methods: Gliomas were profiled using the ArcherDx FusionPlex Assay at a CLIA-certified lab (Caris Life Sciences) and 52 gene targets were analyzed. Fusions with preserved kinase domains were investigated. Results: Among 404 gliomas tested, 39 (9.7%) presented potentially targetable fusions, of which 24/226 (11%) of glioblastoma (GBM), 5/42 (12%) of anaplastic astrocytoma (AA), 2/25 (8%) of grade II astrocytoma and 3 of 7 (43%) of pilocytic astrocytoma (PA) harbored targetable fusions. In GBMs, 1 of 15 (6.7%) IDH-mutated tumors had a fusion while 22 of 175 (12.6%) IDH-wild type tumors had fusions. 46 oligodendroglial tumors were profiled and no fusions were seen, which was lower than frequency of fusions in astrocytic tumors (34/300, p = 0.0236). The most frequent fusions seen involved FGFR3 (N = 12), including 10 FGFR3-TACC3 (1 AA, 6 GBM and 3 glioma NOS); 1 FGFR3-NBR1 (AA) and 1 FGFR3-BRAP (GBM). 11 fusions involving MET were seen, 10 in GBM and 1 in AA. The most common MET fusion was PTPRZ1-MET (1 in AA and 4 in GBM), followed by ST7-MET (N = 3, GBM), CAPZA2-Met (N = 2, GBM) and TPR-MET (N = 1, GBM). 8 NTRK fusions were seen; 1 involving NTRK1 (BCAN-NTRK1, PA), 6 NTRK2 (1 NOS1AP-NTRK2 in AA; GKAP1-NTRK2, KCTD8-NTRK2, TBC1D2-NTRK2 and SOSTM1-NTRK2, 1 each in GBM and 1 VCAN-NTRK2 in grade II astrocytoma) and 1 NTRK3 (EML4-NTRK3 in GBM). EGFR fusions (2 EGFR-SEPT14 and 1 EGFR-VWC2) were seen in 3 GBMs, BRAF in 3 (1 KIAA1549-BRAF, 1 LOC100093631-BRAF in PA and 1 ZSCAN23-BRAF in glioma NOS) and PDGFRA (RAB3IP-PDGFRA, in GBM) in 1. C11orf95-RELA fusions were seen in 2 of 3 grade III ependymomas but not in the 2 grade II ependymomas. Conclusions: We report targetable fusion genes involving NTRK, MET, EGFR, FGFR3, BRAF and PDGFRA including novel fusions that haven’t been previously described in gliomas (e.g., EGFR-VWC2; FGFR3-NBR1). Fusions were seen in over 10% of astrocytic tumors, while none was seen oligodendrogliomas. Identification of such kinase-associated fusion transcripts may allow us to exploit therapeutic opportunities with targeted therapies in gliomas.

Discrimination between low-grade oligodendrogliomas and diffuse astrocytoma with the aid of 11C-methionine positron emission tomography

2011 ◽  
Vol 114 (6) ◽  
pp. 1640-1647 ◽  
Author(s):  
Natsuki Shinozaki ◽  
Yoshio Uchino ◽  
Kyosan Yoshikawa ◽  
Tomoo Matsutani ◽  
Azusa Hasegawa ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Histological Type ◽  
Labeling Index ◽  
Low Grade ◽  
Astrocytic Tumors ◽  
Ki 67 ◽  
Oligodendroglial Tumors ◽  
Grade Ii ◽  
The Mean ◽  
Grade Iii

Object The diagnostic usefulness of 11C-methionine PET scans in gliomas is still controversial. The authors investigated the clinical significance of 11C-methionine PET findings in preoperative diagnosis of histological type and grade. Methods The tissue uptake of 11C-methionine was assessed using PET in 70 patients with histologically confirmed intracerebral gliomas. The ratio of maximum standard uptake values in tumor areas to the mean standard uptake values in the contralateral normal brain tissue (tumor/normal tissue [T/N] ratio) was calculated and correlated with tumor type, histological grade, contrast enhancement on MR imaging, Ki 67 labeling index, and 1p/19q status. Results The T/N ratio was significantly increased as tumor grade advanced in astrocytic tumors (WHO Grade II vs Grade III, p = 0.0011; Grade III vs Grade IV, p = 0.0007). Among Grade II gliomas, the mean T/N ratio was significantly higher in oligodendroglial tumors than in diffuse astrocytomas (DAs) (p < 0.0001). All T/N ratios for oligodendroglial tumors were ≥ 1.46, and those for DA were consistently < 1.46, with the exception of 2 cases of gemistocytic astrocytoma. The Ki 67 labeling index significantly correlated with T/N ratio in astrocytic tumors, but not in oligodendrogliomas. Oligodendroglial tumors without 1p/19q deletion had a significantly higher T/N ratio than those with the codeletion. In combination with Gd-enhanced MR imaging, 67% of nonenhanced tumors with a T/N ratio of ≥ 1.46 were proved to be Grade II oligodendrogliomas. Conclusions These results clearly show that 11C-methionine PET T/N ratios in Grade II oligodendrogliomas were higher than those in DAs independently of their proliferative activity. This information contributes to preoperative differential diagnoses of histological type, especially in suspected low-grade gliomas.

scholarly journals IDHMutations: Genotype-Phenotype Correlation and Prognostic Impact

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Xiao-Wei Wang ◽  
Pietro Ciccarino ◽  
Marta Rossetto ◽  
Blandine Boisselier ◽  
Yannick Marie ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Current Knowledge ◽  
Genomic Alteration ◽  
Prognostic Impact ◽  
Astrocytic Tumors ◽  
Phenotype Correlation ◽  
Good Outcome ◽  
Oligodendroglial Tumors ◽  
Grade Ii ◽  
Grade Iii

IDH1/2mutation is the most frequent genomic alteration found in gliomas, affecting 40% of these tumors and is one of the earliest alterations occurring in gliomagenesis. We investigated a series of 1305 gliomas and showed thatIDHmutation is almost constant in 1p19q codeleted tumors. We found that the distribution ofIDH1R132H,IDH1nonR132H, andIDH2mutations differed between astrocytic, mixed, and oligodendroglial tumors, with an overrepresentation ofIDH2mutations in oligodendroglial phenotype and an overrepresentation ofIDH1nonR132Hin astrocytic tumors. We stratified grade II and grade III gliomas according to the codeletion of 1p19q andIDHmutation to define three distinct prognostic subgroups: 1p19q andIDHmutated,IDHmutated—which contains mostlyTP53mutated tumors, and none of these alterations. We confirmed thatIDHmutation with a hazard ratio = 0.358 is an independent prognostic factor of good outcome. These data refine current knowledge onIDHmutation prognostic impact and genotype-phenotype associations.

Gene fusions evidence in a KIT/PDGFRA wild-type GIST without mutations in SDH units identified by a whole transcriptome study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e21523-e21523
Author(s):  
Milena Urbini ◽  
Annalisa Astolfi ◽  
Valentina Indio ◽  
Maristella Saponara ◽  
Margherita Nannini ◽  
...  
Keyword(s):  
Gene Fusion ◽  
Surgical Removal ◽  
Erk Pathway ◽  
Gene Fusions ◽  
Rna Seq ◽  
Wild Type ◽  
Rna Pol Ii ◽  
Molecular Events ◽  
Frame Fusion ◽  
Whole Transcriptome

e21523 Background: A subset of KIT/PDGFRA wild-type GIST (WT) harbour mutations in SDH units. In the majority of the remaining cases of WT GIST no other molecular events are identified.We performed a RNA-seq in a WT GIST without mutations in SDH genes using next generation approach to discover molecular events in this GIST population. Methods: In 2003, a 63-year old woman underwent surgery for an ileal GIST (size 6 cm, MI 6/50HPF).After 6 years, she developed a recurrence with a single hepatic lesion. The KIT and PDGFRA analysis of the lesion did not show mutations. Therefore, she did not receive imatinib but she underwent a surgical removal. The analysis of all SDH units did not show mutations. So paired-end RNA-seq (75X2) was performed with Illumina HiScanSQ platform. After mapping the short reads on the human genome(HG19), SNVs and InDels were called by SNVMix2 with an accurate filtering procedures including predictors of mutations effect at protein level. Gene fusions discovery was done considering the agreement between DeFuse, ChimeraScan and FusionMap tools and validated by SangerSequencing using primers spanning the mRNA breakpoints. Results: Four different gene fusions and 206 non-synonymous SNVs were discovered, of which 62 were called deleterious by at least one predictor, and they are undergoing further validation. SPRED2-NELFCD gene fusion originated from an interchromosomal translocation-inversion between chr 20 and 2. The event involved exon1 of SPRED2 and exon11 of NELFCD, probably leading to inactivation of both genes. NELFCD encodes a component of the NELF complex that negatively regulates transcription elongation by RNA pol II, while SPRED2 is a member of the Sprouty /SPRED family that repress growth factor-induced activation of the MAPK/ERK pathway. The other three events were intrachromosomal aberrations: MARK2-PPFIA1 and PLA2G16-ATL3 on chr 11 and ASCC1-C10orf11 on chr 10. Only the first event led to an in-frame fusion (MARK2 ex1- PPFIA1 ex2) probably dysregulating the expression of the downstream gene. Conclusions: This is the first evidence of gene fusions in GIST. The oncogenetic role and the tumor frequency of these events deserve to be studied.

A phase II trial of temozolomide (TMZ) 1 week on/1 week off as initial treatment for high risk low grade oligodendroglial tumors: An AINO (Italian Association for Neuro-Oncology) study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2026-2026
Author(s):  
Roberta Ruda ◽  
Alessia Pellerino ◽  
Federica Franchino ◽  
Andrea Pace ◽  
Carmine Maria Carapella ◽  
...  
Keyword(s):  
Phase Ii ◽  
Seizure Control ◽  
Tumor Response ◽  
Low Grade ◽  
Significant Activity ◽  
Wild Type ◽  
Oligodendroglial Tumors ◽  
Response To Chemotherapy ◽  
Grade Ii ◽  
Dose Dense

2026 Background: The efficacy of dose-dense temozolomide (TMZ, 1 week on/1 week off ) in grade II gliomas is not well known and could depend on the molecular subtype. Methods: Between 2006 and 2010 a single arm phase II study on 60 patients with grade II oligodendroglial tumors was performed. Inclusion criteria were as follows: 1) age ≥ 18 years; 2) KPS ≥ 70; 3) biopsy-proven grade II oligodendroglioma or oligoastrocytoma ; 4) a measurable residual tumor after surgery. The primary endpoint was tumor response on MRI according to RANO criteria, while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and seizure control. Most patients (65%) had seizures. Molecular factors (IDH 1-2 mutations, 1p19q codeletion, MGMT methylation) were available in 49/60 patients (81.7%). The median number of cycles was 11 (2-18). Median follow up was 64 months (7-112). Results: Response rate was PR in 21/60 (35%) patients, minor PR (mPR) in 14/60 (23%), SD in 21/60 (35%) and PD in 4/60 (7%). Most patients achieved the best tumor response within 6 months after the start of TMZ. Among patients with mPR and PR, 15/49 (30.6%) were IDH1-2 mutated with a PFS of 71.4% at 36 months and 28.6% at 60 months with a median value of 46 months while 11/49 (22.4%) were IDH 1-2 wild-type with a PFS of 45.8% at 36 months and 25% at 60 months with a median value of 34 months. OS was 90.5% at 36 months and 66.7% at 60 months with a median value of 76 months in the IDH1-2 mutated/1p19q codeleted subgroup, while OS was 66.7% at 36 months and 50% at 60 months with a median value of 60 months in the IDH1-2 wild-type subgroup. Responses were higher in MGMT methylated patients. Seizure improvement was achieved in 29/34 patients (85%): 17/33 (52%) patients at 12 months and 18/29 (62.1%) at 24 months were seizure-free. Time to maximal seizure response was earlier than that observed on MRI (3 vs 6 months). Conclusions: Dose-dense TMZ has shown a significant activity in terms of tumor and seizure control, especially in IDH1-2 mutated/1p19q codeleted patients. Seizure reduction could represent an early indicator of response to chemotherapy and maybe predict the duration of response. Clinical trial information: 2007-000386-38.

scholarly journals The landscape of gene fusions in hepatocellular carcinoma

2016 ◽  
Author(s):  
Chengpei Zhu ◽  
Yanling Lv ◽  
Liangcai Wu ◽  
Jinxia Guan ◽  
Xue Bai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Progression ◽  
Gene Fusion ◽  
Early Stage ◽  
Pcr Analysis ◽  
Gene Fusions ◽  
Fusion Genes ◽  
Rna Seq ◽  
Rt Pcr ◽  
Critical Function

AbstractMost hepatocellular carcinoma (HCC) patients are diagnosed at advanced stages and suffer limited treatment options. Challenges in early stage diagnosis may be due to the genetic complexity of HCC. Gene fusion plays a critical function in tumorigenesis and cancer progression in multiple cancers, yet the identities of fusion genes as potential diagnostic markers in HCC have not been investigated.Paired-end RNA sequencing was performed on noncancerous and cancerous lesions in two representative HBV-HCC patients. Potential fusion genes were identified by STAR-Fusion in STAR software and validated by four publicly available RNA-seq datasets. Fourteen pairs of frozen HBV-related HCC samples and adjacent non-tumor liver tissues were examined by RT-PCR analysis for gene fusion expression.We identified 2,354 different gene fusions in the two HBV-HCC patients. Validation analysis against the four RNA-seq datasets revealed only 1.8% (43/2,354) as recurrent fusions that were supported by public datasets. Comparison with four fusion databases demonstrated that three (HLA-DPB2-HLA-DRB1, CDH23-HLA-DPB1, and C15orf57-CBX3) out of 43 recurrent gene fusions were annotated as disease-related fusion events. Nineteen were novel recurrent fusions not previously annotated to diseases, including DCUN1D3-GSG1L and SERPINA5-SERPINA9. RT-PCR and Sanger sequencing of 14 pairs of HBV-related HCC samples confirmed expression of six of the new fusions, including RP11-476K15.1-CTD-2015H3.2.Our study provides new insights into gene fusions in HCC and could contribute to the development of anti-HCC therapy. RP11–476K15.1-CTD–2015H3.2 may serve as a new therapeutic biomarker in HCC.

scholarly journals Fusion detection and quantification by pseudoalignment

2017 ◽  
Author(s):  
Páll Melsted ◽  
Shannon Hateley ◽  
Isaac Charles Joseph ◽  
Harold Pimentel ◽  
Nicolas Bray ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosomal Rearrangements ◽  
Clinical Use ◽  
Gene Fusions ◽  
Fusion Genes ◽  
Rna Seq ◽  
Sequencing Data ◽  
Transcript Quantification ◽  
Novel Approach ◽  
Fusion Detection

RNA sequencing in cancer cells is a powerful technique to detect chromosomal rearrangements, allowing for de novo discovery of actively expressed fusion genes. Here we focus on the problem of detecting gene fusions from raw sequencing data, assembling the reads to define fusion transcripts and their associated breakpoints, and quantifying their abundances. Building on the pseudoalignment idea that simplifies and accelerates transcript quantification, we introduce a novel approach to fusion detection based on inspecting paired reads that cannot be pseudoaligned due to conflicting matches. The method and software, called pizzly, filters false positives, assembles new transcripts from the fusion reads, and reports candidate fusions. With pizzly, fusion detection from raw RNA-Seq reads can be performed in a matter of minutes, making the program suitable for the analysis of large cancer gene expression databases and for clinical use. pizzly is available at https://github.com/pmelsted/pizzly

Comprehensive assessment of ATRX mutation, protein expression, and alternative lengthening of telomeres (ALT) phenotype in grade II and III gliomas.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2064-2064 ◽  
Author(s):  
Aline P. Becker ◽  
Erica Hlavin Bell ◽  
Jessica Fleming ◽  
Joseph P McElroy ◽  
Denise Fabian ◽  
...  
Keyword(s):  
Protein Expression ◽  
Point Mutations ◽  
Small Sample ◽  
Wild Type ◽  
Idh1 R132h ◽  
Long Term Follow Up ◽  
Grade Ii ◽  
The Ohio State University ◽  
Small Sample Sizes ◽  
Grade Iii

2064 Background: ATRX mutations are key molecular markers for classification of gliomas. We aimed to evaluate ATRXmutations and protein expression and the ALT phenotype as potential biomarkers for grade II and III gliomas. Methods: Retrospective analysis of 156 adult gliomas, with long-term follow up. Gene sequencing ( IDH1/2 and ATRX), Oncoscan array (1p19q co-deletion), FISH assays (1p19q co-deletion and ALT phenotype) and immunohistochemistry (IDH1 R132H and ATRX) were performed and the results were correlated with OS and PFS. Results: Twenty-six out of 94 samples (27.7%) had ATRX mutations, commonly related to IDH1/2 mutant-1p/19q intact tumors (22/26 cases – p < 0.0001), however, 3 (11.5%) mutant tumors had concurrent 1p/19q co-deletions. ATRX loss of expression occurred in 66/150 cases (44%), consistently related to ATRX mutations (p < 0.0001). Intriguingly, 4/25 ATRX mutant tumors (2 frameshift and 2 point mutations with low/medium functional impact) showed weak/heterogeneous expression, while 18/65 (27.7%) ATRX wild type tumors had loss of protein expression. ALT phenotype was detected in 50/150 cases (33.3%), strongly related to ATRX mutations (23/32 cases), loss of protein expression (45/50 cases), and to IDH1/2 mutant-1p/19q intact tumors (35/41 cases). Two ATRX mutant tumors were ALT negative, while nine ATRX wild type tumors with loss of expression had ALT phenotype. ATRXmutations, loss of protein expression, and ALT phenotype were strongly related to longer OS in grade III gliomas (p = 0.006, 0.023 and 0.003, respectively). Further subset analyses were not completed due to small sample sizes. Conclusions: ATRX mutations and loss of protein expression as well as ALT phenotype are potential prognostic factors for grade III gliomas. Importantly, this study highlights possible discrepancies (although infrequent) between ATRX sequencing, immunohistochemistry, and FISH (ALT). In addition, other mechanisms of ATRX gene silencing should be further investigated in grade II and III gliomas. FUNDING: R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01 (NCI), Brain Tumor Funders Collaborative Grant, and The Ohio State University CCC (all to AC).

scholarly journals PATH-61. IMMUNOHISTOCHEMICAL PHENOTYPING AND SURVIVAL ANALYSIS OF WHO GRADE II-IV GLIOMAS

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi157-vi157
Author(s):  
Nora Poulos ◽  
Srikar Sattiraju ◽  
Charles Opalak ◽  
Mikhail Dozmorov ◽  
Jason Harrison ◽  
...  
Keyword(s):  
Overall Survival ◽  
Wilms Tumor ◽  
Positive Staining ◽  
High Grade ◽  
Wild Type ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade ◽  
Clinical Prognosis ◽  
Grade Ii ◽  
Grade Iii

Abstract INTRODUCTION Specific genetic mutations are linked to clinical prognosis in gliomas. There has been increasing demand to understand the association between tissue biomarker expression and survival. Using patient-derived samples, WHO grade II-IV gliomas were evaluated by the protein-staining pattern of molecular markers of interest across tumor grade, and the association between their expression and survival was investigated. METHODS Tissue microarrays (TMA) containing duplicate 1 mm cores were generated from 78 gliomas (WHO grade II-IV) using an automated TMA system. Immunohistochemistry was performed per the manufactures recommendation to evaluate expression of: Wilms tumor 1 (WT1), platelet endothelial cell adhesion molecule (CD31), adhesion G protein-coupled receptor E5 (CD97), complement decay-accelerating factor (CD55), hypoxia inducible factor 1 subunit alpha (HIF1α), EGF-like module-containing mucin-like hormone receptor-like 3 (EMR3), integrin, and isocitrate dehydrogenase 1 (IDH1). Samples with moderate (+1) or intense (+2) staining to WT1, CD31, CD97, CD55, or HIF1α, or any staining to EMR3 or IDH1 mutation, were considered positive. RESULTS Of the 78 tumor samples, there were 11 (14%) WHO grade II, 22 (28%) grade III, and 45 (59%) grade IV gliomas. Across grade III gliomas, anaplastic astrocytomas had significantly higher positive WT1 (p=0.04), CD31 (p=0.002) and IDH1 wild-type (p< 0.0001) staining. High-grade (III & IV) gliomas had significantly higher positive staining for WT1 (p=0.013), CD31 (0.024), integrin (p=0.021), and IDH1 wild type (p=0.044). In all gliomas, positive staining for WT1 (p< 0.0001), CD31 (p=0.009), CD97 (p=0.024), EMR3 (p=0.036), and IDH1 wild type (p=0.0006) were associated with worse overall survival. After adjusting for patient age, positive staining for WT1 (p=0.003) was associated with worse overall survival. CONCLUSION Using immunohistochemistry, unique biomarker staining patterns were identified for WHO grade III anaplastic astrocytomas and for high-grade gliomas. Irrespective of grade, staining for WT1, CD97, CD31, EMR3, and IDH1 wild-type were associated with worse overall survival.

scholarly journals Re-Evaluate Fusion Genes in Prostate Cancer

2021 ◽  
Vol 20 ◽  
pp. 117693512110275
Author(s):  
Ting Wei ◽  
Ji Lu ◽  
Tao Ma ◽  
Haojie Huang ◽  
Jean-Pierre Kocher ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
The Cancer Genome Atlas ◽  
Gene Fusions ◽  
Fusion Genes ◽  
Rna Seq ◽  
Protein Coding ◽  
Pten Deletion ◽  
Cancer Genome Atlas ◽  
Receptor Signaling Pathway ◽  
Ets Family

Background: Thousands of gene fusions have been reported in prostate cancer, but their authenticity, incidence, and tumor specificity have not been thoroughly evaluated, nor have their genomic characteristics been carefully explored. Methods: We developed FusionVet to dedicatedly validate known fusion genes using RNA-seq alignments. Using FusionVet, we re-assessed 2727 gene fusions reported from 36 studies using the RNA-seq data generated by The Cancer Genome Atlas (TCGA). We also explored their genomic characteristics and interrogated the transcriptomic and DNA methylomic consequences of the E26 transformation-specific (ETS) fusions. Results: We found that nearly two-thirds of reported fusions are intra-chromosomal, and 80% of them were formed between 2 protein-coding genes. Although most (76%) genes were fused to only 1 partner, we observed many fusion hub genes that have multiple fusion partners, including ETS family genes, androgen receptor signaling pathway genes, tumor suppressor genes, and proto-oncogenes. More than 90% of the reported fusions cannot be validated by TCGA RNA-seq data. For those fusions that can be validated, 5% were detected from tumor and normal samples with similar frequencies, and only 4% (120 fusions) were tumor-specific. The occurrences of ERG, ETV1, and ETV4 fusions were mutually exclusive, and their fusion statuses were tightly associated with overexpressions. Besides, we found ERG fusions were significantly co-occurred with PTEN deletion but mutually exclusive with common genomic alterations such as SPOP mutation and FOXA1 mutation. Conclusions: Most of the reported fusion genes cannot be validated by TCGA samples. The ETS family and androgen response genes were significantly enriched in prostate cancer–specific fusion genes. Transcription activity was significantly repressed, and the DNA methylation was significantly increased in samples carrying ERG fusion.

scholarly journals The Fusion Gene Landscape in Taiwanese Patients with Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1343
Author(s):  
Ya-Sian Chang ◽  
Siang-Jyun Tu ◽  
Ju-Chen Yen ◽  
Ya-Ting Lee ◽  
Hsin-Yuan Fang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Fusion Gene ◽  
Small Cell ◽  
Gene Fusions ◽  
Fusion Genes ◽  
Rna Seq ◽  
Small Cell Lung ◽  
Driver Genes ◽  
Cancer Driver

Background: Analyzing fusion gene transcripts may yield an effective approach for selecting cancer treatments. However, few comprehensive analyses of fusions in non-small cell lung cancer (NSCLC) patients have been performed. Methods: We enrolled 54 patients with NSCLC, and performed RNA-sequencing (RNA-Seq). STAR (Spliced Transcripts Alignment to a Reference)-Fusion was used to identify fusions. Results: Of the 218 fusions discovered, 24 had been reported and the rest were novel. Three fusions had the highest occurrence rates. After integrating our gene expression and fusion data, we found that samples harboring fusions containing ASXL1, CACNA1A, EEF1A1, and RET also exhibited increased expression of these genes. We then searched for mutations and fusions in cancer driver genes in each sample and found that nine patients carried both mutations and fusions in cancer driver genes. Furthermore, we found a trend for mutual exclusivity between gene fusions and mutations in the same gene, with the exception of DMD, and we found that EGFR mutations are associated with the number of fusion genes. Finally, we identified kinase gene fusions, and potentially druggable fusions, which may play roles in lung cancer therapy. Conclusion: The clinical use of RNA-Seq for detecting driver fusion genes may play an important role in the treatment of lung cancer.

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